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Susceptibility of Rickettsia rickettsii to Tigecycline in a Cell Culture Assay and Animal Model for Rocky Mountain Spotted Fever

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  • 1 Department of Internal Medicine–Infectious Diseases, University of Texas Medical Branch, Galveston, Texas;
  • | 2 School of Medicine, University of Texas Medical Branch, Galveston, Texas;
  • | 3 Department of Pathology, University of Texas Medical Branch, Galveston, Texas

Rocky Mountain spotted fever (RMSF), caused by Rickettsia rickettsii, is a severe tick-borne infection endemic to the Americas. Oral doxycycline is effective, but during severe life-threatening disease, intravenous therapy is recommended. Unfortunately, intravenous formulations of doxycycline are not always available. Therefore, we aimed to determine the susceptibility of R. rickettsii to an alternative parenteral agent, tigecycline, in vitro and in vivo. To determine the minimum inhibitory concentration of tigecycline, R. rickettsii–inoculated Vero cells were incubated with medium containing tigecycline. At various time points, monolayers were collected and R. rickettsii was quantified via real-time polymerase chain reaction (PCR). The growth of R. rickettsii was inhibited in the presence of ≥ 0.5 µg/mL of tigecycline. To determine the effectiveness of tigecycline in vivo, guinea pigs were inoculated with R. rickettsii. Five days after inoculation, they were treated twice daily with subcutaneous tigecycline 3.75 mg/kg or subcutaneous doxycycline 5 mg/kg. Treated animals improved, whereas untreated controls remained ill. Tissues were collected for quantitative PCR–determined bacterial loads on day 8. Median bacterial loads in the tigecycline group were less than those in untreated animals: liver (0 versus 2.9 × 104 copies/mg), lung (0 versus 8.3 × 103 copies/mg), skin (2.6 × 102 versus 2.2 × 105 copies/mg), spleen (0 versus 1.3 × 104 copies/mg), and testes (0 versus 1.0 × 105 copies/mg, respectively). There were no significant differences in the bacterial loads between doxycycline-treated versus tigecycline-treated guinea pigs. These data indicate that tigecycline is effective against R. rickettsii in cell culture and in an animal model of RMSF.

Author Notes

Address correspondence to Lucas S. Blanton, Department of Internal Medicine–Infectious Diseases, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555. E-mail: lsblanto@utmb.edu

Financial support: L. S. B. is supported by the Institute for Translational Sciences at the University of Texas Medical Branch, supported in part by a CTSA Mentored Career Development (KL2) Award (KL2TR001441) from the National Center for Advancing Translational Sciences, National Institutes of Health. This work was also supported by the Carmage and Martha Walls Distinguished University Chair in Tropical Diseases Endowment.

Authors’ addresses: Lucas S. Blanton and Bethany R. Quade, Department of Internal Medicine–Division of Infectious Diseases, University of Texas Medical Branch, Galveston, TX, E-mails: lsblanto@utmb.edu and bequade@utmb.edu. Nicholas M. Wilson, School of Medicine, University of Texas Medical Branch, Galveston, TX, E-mail: nmwilson@utmb.edu. David H. Walker, Department of Pathology, University of Texas Medical Branch, Galveston, TX, E-mail: dwalker@utmb.edu.

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